The Effect Of NGF On CCL₄-induced Hepatic Fibrosis In Mice And Its Mechanism

Objective: To observe the effect of nerve growth factor on CCL4-inducedhepatic fibrosis in mice and study its mechanism of preventing hepatic fibrosis.Methods: Hepatic fibrosis model was induced by subcutaneous injection ofCCL4in mice. Thirty female Kun Ming mice were equally and randomly divided intothree groups: fibrosis model group (A), NGF treatment group (B) and normal group(C). Eight weeks following the initiation of experiment, samples were collected tomeasure ALT,AST, TBIL, ALB, evaluate liver fibrosis indices(HA, LN, PCIII，IVC),observe liver tissues and pathological changes (HE staining, reticular fiber stainingand masson staining) and use Ishaki scoring system to assess the severity of hepaticinflammation and fibrosis. The expression of Bax gene in mouse liver tissues wasshowed by Semi-quantitative RT-PCR analysis. The experiment data were processedby SPSS18.0statistical software．Results: Hepatic fibrosis was successfully induced by CCL4, and significantfibrosis around the portal area and formation of spiky fibers and fibrous septa wereobserved. Serum levels of ALT, AST, HA and LN in group A, B were significantlyhigher than in group C (F=111.45,658.80,157.43,167.99; all P<0.05), and group Bwas significantly lower than group A (P<0.05). HE staining, reticular fiber stainingand masson staining showed that compared to group A, Liver fibrosis andinflammation in group B was relieved significantly. There were no inflammatory cellsand fibers in group C. And seen from the Ishaki scoring system for assessment of theseverity of hepatic inflammation, the number of mice in group A were respectively0scored0-3points,0scored4-6points,3scored7-9points,6scored10-14points,1scored15-18points, in group B were respectively0,2,7,1,0and it were10,0,0,0,0ingroup C. Similarly for hepatic fibrosis, the number of mice in group A wererespectively0,0,2,2,4,2from0point to6points, it were0,1,6,3,0,0in group B and itwere7,3,0,0,0in group C. After statistics analysis, there were differences betweengroupA, B (P<0.05). Semi-quantitative RT-PCR analysis showed that the absorbance ratio of Bax/β-actin in group A, B, C were (0.677±0.193),(1.234±0.027),(1.525±0.037). According to statistical analysis, there was significant differenceamong each group (P<0.05).Conclusions: NGF can effectively prevent hepatic fibrosis induced by CCL4andrelieve liver inflammation via a mechanism associated with relieving liverinflammation and up-regulating Bax gene expression in hepatic tissue.